Year
2025
Principal Investigator
Principal Investigator
Platform 1
Platform 2
Location
Italy, IT
Abstract
The project will validate a novel lead compound against solid tumors based on copper (II) nitroprusside, a nitric oxide donor containing dual Fenton initiator metals (Cu and Fe) able to generate reactive oxygen (ROS) and peroxynitrite (ONOO-) species at tumoral sites, exhibiting a potent cytotoxicity against various types of tumor cells. This novel lead compound, patented by prof. Rizzolio’s group, was specifically designed to overcome the two main issues of ChemoDynamic Therapy (CDT): the small amount of endogenous hydrogen peroxide, and the smaller number of cations produced from the catalyst to initiate Fenton like reactions. CDT uses the tumor microenvironment to activate Fenton/Fenton-like reactions to generate strong oxidative hydroxyl radicals for tumor treatment. The advantages of the proposed approach are the following: high selectivity, no limitation in tissue penetration and negligible damage to normal tissues. Main goal of the project is to evaluate the efficacy and toxicity of the pharmaceutical formulations exploiting an organ-on-chip model of the ovarian cancer microenvironment, and to cross-validate the in vitro results with those obtained in the animal model (by CRO-Aviano).
Objectives
- Objective 1 - Develop an in vitro model of the ovarian cancer microenvironment
- Objective 2 – Apply the model to determine the efficacy and toxicity of copper nitroprusside nanoformulations
- Objective 3 – Compare and contrast in vitro data with those obtained in vivo in the animal model.
Collaborators
- Flavio Rizzolio (Univ. Ca’ Foscari di Venezia & CRO Aviano - IRCCS)
- Isabella Caligiuri (CRO Aviano)
- Debora Basile (Ospedale S. Giovanni di Dio, Crotone)
Key 5 publications
- 1. S. Giannitelli, V. Peluzzi, S. Raniolo, G. Roscilli, M. Trombetta, P. Mozetic, A. Rainer. On- chip recapitulation of the tumor microenvironment: A decade of progress. Biomaterials 306 (2024) 122482.
- 2. E. Limiti, P. Mozetic, S.M. Giannitelli, F. Pinelli, X. Han, D.Del rio, F. Abbruzzese, F. Basoli, L. Rosanò, S. Scialla, M. Trombetta, G. Gigli, Z.J. Zhang, E. Mauri, A. Rainer, Hyaluronic Acid-Polyethyleneimine Nanogels for Controlled Drug Delivery in Cancer Treatment. ACS Appl. Nano Mater. 5 (2022) 5544-5557.
- 3. I. Masi, V. Caprara, F. Spadaro, L. Chellini, R. Sestito, A. Zancla, A. Rainer, A. Bagnato, L. Rosanò. Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK. Cell Rep 34 (2021) 108800.
- 4. V. Lucarini, C. Buccione, G. Ziccheddu, F. Peschiaroli, P. Sestili, R. Puglisi, G. Mattia, C. Zanetti, I. Parolini, L. Bracci, I. Macchia, A. Rossi, M.T. D’Urso, D. Macchia, M. Spada, A. De Ninno, A. Gerardino, P. Mozetic, M. Trombetta, A. Rainer, L. Businaro, G. Schiavoni, F. Mattei, Combining Type I Interferons and 5-Aza-2’-Deoxycitidine to Improve Anti- Tumor Response against Melanoma. J. Invest. Dermatol. 137 (2017) 159.
People
- Alessandra Zizzari (CNR-NANOTEC)
- Pamela Mozetic (CNR-NANOTEC)
- Elisa De Luca (CNR-NANOTEC)
- Monica Bianco (CNR-NANOTEC)
- Elisabetta Perrone (CNR-NANOTEC)
- Enrico Lemma (UCBM, Associato NANOTEC)
- Ermanno Cordelli (UniSalento, Associato NANOTEC)
- Vita Guarino (UniSalento, Associata NANOTEC)
- Chiara Coricciati (UCBM, Associato NANOTEC)